PSEN1, PSEN2, and APP mutations in 404 Chinese pedigrees with familial Alzheimer's disease

Alzheimers Dement. 2020 Jan;16(1):178-191. doi: 10.1002/alz.12005.

Abstract

Introduction: The PSENs/APP mutation distribution in Chinese patients with familial Alzheimer's disease (FAD) remains unclear. We aimed to analyze the genetic features of Chinese FAD pedigrees with and without PSENs/APP mutations.

Methods: In total, 1330 patients with Alzheimer's disease (AD) or mild cognitive impairment in 404 pedigrees were enrolled from the Chinese Familial Alzheimer's Disease Network. PSENs/APP mutations and APOE frequencies were determined.

Results: In total, 13.12% of pedigrees carried PSENs/APP missense mutations, 3.71% carried PSENs/APP synonymous/untranslated region variants, and 83.17% did not carry PSENs/APP mutations. Eleven missense mutations were first identified. In patients without PSENs/APP mutations, 44.31% carried one APOEε4 allele, and 14.85% two APOEε4 alleles.

Discussion: The new PSENs/APP mutations indicate heterogeneity in AD pathogenesis between Chinese and other ethnic groups. The low mutation rate suggests the involvement of other genes/factors in Chinese FAD. APOEε4 might be a major gene for some FAD without PSENs/APP mutations.

Keywords: APOEε4; Alzheimer's disease; PSENs/APP mutations; familial Alzheimer's disease; mild cognitive impairment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Alzheimer Disease / genetics*
  • Amyloid beta-Protein Precursor / genetics*
  • Asian People*
  • China
  • Female
  • Humans
  • Male
  • Mutation, Missense
  • Pedigree*
  • Presenilin-1 / genetics*
  • Presenilin-2 / genetics*

Substances

  • APP protein, human
  • Amyloid beta-Protein Precursor
  • PSEN1 protein, human
  • PSEN2 protein, human
  • Presenilin-1
  • Presenilin-2